During the coming year we propose to carry out studies in the following areas: 1. Isolate, purify and characterize the actinomycin analogues that are produced in the presence of cis- or trans-4-chloroproline and to determine some of the biological activities of the new antibiotics. 2. To continue studies on the nature of the amino acid components of novel actinomycins such as those of the Z series. 3. To carry out investigations on the biogenesis of the unusual amino acids (e.g., N-methylamino acids, D-amino acids, amino acids) in the actinomycins. 4. To study the biosynthesis of the actinomycin molecule employing cell-free systems. 5. To initiate studies (genetic, biochemical) to establish the role of tryptophan metabolism in the biosynthesis of the actinomycin chromophore, actinocin.